Does prophylactic sotalol and magnesium decrease the incidence of atrial fibrillation following coronary artery bypass surgery: a propensity-matched analysis

Background  

Atrial fibrillation can occur in up to 40% of patients undergoing coronary surgery.     

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.     

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 2: Ring-Substituted Derivatives

A range of 18 derivatives of flavone-8-acetic acid (FAA) with substituents on the 2-phenyl group have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. There was no clear-cut relationship between in vitro and in vivo activity but the activity in each situation was found to be very sensitive to the precise substitution pattern with closely related isomers giving widely different activities. Some of the compounds, notably 10b,cj , and r , were active in vivo and these require further studies in order to evaluate their potential for development.     

Factors involved in the anti-cancer activity of the investigational agents LM985 (flavone acetic acid ester) and LM975 (flavone acetic acid)

LM985 has been shown previously to hydrolyse to flavone acetic acid (LM975) in mouse plasma and to produce significant anti-tumour effects in transplantable mouse colon tumours (MAC). It has undergone Phase I clinical trials and dose limiting toxicity was acute reversible hypotension. Substantially higher doses of LM975 can be given clinically without dose limiting toxicity. We have investigated the activity of LM975 against a panel of MAC tumours and also the in vitro cytotoxicity of both LM985 and LM975 in two cell lines derived from MAC tumours. LM985 is considerably more cytotoxic than LM975 in vitro but increased length of exposure to LM975 results in improved activity. Single in vivo injection of LM975 showed no activity against the ascitic tumour MAC 15A, moderate activity against the s.c. poorly differentiated tumour MAC 13 and produced a significant growth delay in the well differentiated MAC 26. These latter responses were considerably enhanced by repeated injection 7 days later. Pharmacokinetic studies in mice following i.p. injection of LM985 demonstrated rapid degradation of LM985 to LM975 in the peritoneum. Length of exposure as well as drug concentration appear important factors in determining anti-tumour responses.     

A randomized controlled trial of sedation in the critically ill

A randomized controlled trial comparing: a) a combination of oral chloral hydrate and promethazine to b) a continuous intravenous midazolam infusion, for maintenance sedation in critically ill children, was carried out. The level of sedation was assessed four hourly using a specifically devized sedation scale. Forty-four children entered the study of whom two were subsequently excluded. The number of satisfactory assessments (desired and actual levels of sedation equal) was significantly greater in the chloral hydrate and promethazine group (Chi-squared P <0.01; confidence intervals of the difference 0.06 to 0.20). The number of assessments at level 5 on the sedation scale (patient restless/distressed) was significantly greater in the midazolam group (Chi-squared P <0.05). The total number of satisfactory assessments in the two groups were only 61 and 48% respectively, suggesting that sedation can be considerably improved. Chloral hydrate and promethazine are more effective than midazolam as maintenance sedation in critically ill children. It is possible to prospectively study the efficacy of sedative drugs in critically ill children.     

Nucleoside analogues: 8. Some isomers of B.3839, the original 5-fluorouracil/nitrosourea molecular combination, and their effect on colon, breast and lung tumours in mice

This study describes the manipulation of secondary products arising from the synthesis of the prototypical molecular combination of 5-fluorouracil (5-FU) and chloroethylnitrosourea (CNU), B.3839, in order to investigate the effects produced by connecting the C-S-C-C-CNU chain to the 5-FU ring in different ways. The isolation of phthalimide precursors of these compounds and the transformation into CNUs is described. Anti-tumour activity of these molecular combinations against a series of experimental murine colon, lung and mammary tumours is presented. The spectrum of anti-tumour activity displayed is interesting but defies simple explanation without further detailed in vivo pharmacokinetic and metabolism studies in order to define optimal profiles for activity.     

Auditing your acute pain service—a UK NHS model

This audit has been conducted in order to provide an evidence base that clarifies the strengths and weaknesses of acute pain management at a UK hospital. Consequently, it sets the strategic direction for service improvement. Awarding up to three stars has identified the quality of each component that constitutes the acute pain service. Six different components were audited and star ratings have been awarded as shown below:

• Pain tool (including patient and staff understanding): no stars.

• Pain team (including education and clinical support): two stars.

• Intermittent opioid analgesia (sub-cut and oral morphine): two stars.

• Epidural patient controlled analgesia (EPCA): two stars.

• Intravenous patient controlled analgesia (IVPCA): two stars.

• Single-dose intrathecal opioid analgesia: three stars.

These star ratings were pulled together in order to award the acute pain service an overall rating. Consequently, the acute pain service was awarded two stars. The findings of this audit identify that this acute pain service provides a safe way to deliver hi-tech pain relief at ward level and can be relied upon to provide good quality pain management. However, too many patients are likely to miss out on the full benefits of the service due to the weaknesses as identified. The quality of the pain relief is impeded across the hospital due to low patient expectation and poor patient education, and also due to a lack of relevant knowledge amongst nursing staff. Developments in the role of the acute pain nurse, staff training and education programs, and a reduction in the variety of pain management pumps are combining to facilitate the opportunities required to address the weaknesses and to build on the strengths of the acute pain service.